Efficacy of Immunization With 4C-MenB in Preventing Experimental Urethral Infection With Neisseria Gonorrhoeae

• Status: Not yet recruiting
• Trial end date: 2028-02-01
• Target enrollment: 0
• Participant gender: Male

Summary

This is a double-blind randomized controlled trial to test whether the group B meningitis vaccine 4 component Neisseria meningitidis serogroup B vaccine (BEXSEROTM) (4C-MenB), trade name Bexsero™), currently approved for use by the United States Food and Drug Administration (FDA) and recommended by the Centers for Disease Control and Prevention (CDC) for protection from Neisseria meningitidis infections, also protects from Neisseria gonorrhoeae infection using controlled human experimental infection to test protection. The information the investigator learn by doing this study may also help to develop a vaccine that protects individuals from having gonorrhea infection.

The study population will consist of male participants > 18 and < 36 years old, living in central North Carolina, in general good health without a history of 4C-MenB vaccination. Approximately 120-140 participants will be enrolled.

Participants will receive 2 doses of vaccine (2 doses of 4C-MenB or 2 comparator vaccines- seasonal influenza and tetanus/diptheria booster) as intramuscular injections, and then one intraurethral challenge with Neisseria gonorrhoeae. Following the challenge, participants will cross-over and receive two doses of vaccines not received prior to challenge (2 doses of 4CMenB or the 2 comparator vaccines- seasonal influenza and tetanus/diptheria booster) All participants receive all vaccinations by the end of the study and all vaccines used in this study are licensed and FDA-approved.

• Phase: Phase 2
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: University of North Carolina, Chapel Hill
• Collaborator: National Institute of Allergy and Infectious Diseases (NIAID)
• Treatments: Cefixime; Ceftriaxone; Ciprofloxacin; Vaccines

Criteria

Inclusion Criteria:

Participants must meet all the inclusion criteria to participate in the study.

• Assigned male at birth and now ≥ 18 and < 36 years old

• No history of prior Neisseria meningitidis serogroup B (MenB) vaccination

• Able and willing to be located easily by providing street address and telephone number (land line and/or cell phone number)

• Willingness to provide written informed consent

• Informed consent obtained and signed

• Able and willing to attend all study visits

• Able and willing to abstain from all sexual activity involving contact with the participant's penis, urine, or semen and a person other than the participant during experimental gonococcal infection phase until the follow-up test for gonorrhea is negative

• Able and willing to abstain from scheduled immunizations other than those provided through the study, between enrollment and completion of Ng challenge.

• No clinically significant abnormalities on physical exam

• Urinalysis: leukocyte esterase and WBC values within normal limits

• 50% complement hemolytic activity (CH50) within normal limits (WNL)

• Negative HIV and syphilis test results at the screening visit

• Denies history of bleeding diathesis

• Denies history of seizures (due to reports of seizures with ciprofloxacin), history of childhood febrile seizure acceptable

• Denies history of cancer, except basal cell carcinoma of the skin >5 years ago

• Denies current drug abuse that would interfere with study activities

• Denies history of penile, urethral, prostate, testis and associated structures surgery (varicocele repair, vasectomy, and vasectomy repair are acceptable if greater than 1 year prior to enrollment)

Exclusion Criteria:

Participants meeting any of the exclusion criteria at initial screening and screening prior to Ng challenge will be excluded from study participation. If the results of Complete blood count (CBC), serum alanine transaminase (ALT), serum creatinine, or urinalysis obtained at initial screening are outside acceptable limits, and the clinician judges the deviation unlikely to be clinically relevant, one-time repeat screening is permitted. Acceptable laboratory values are presented in Appendix B.15

• Student or employee under the direct supervision of any of the study investigators

• Any known immunodeficiencies, including complement deficiency, antibody deficiency, chronic granulomatous disease or HIV infection

• A history of prior confirmed N. meningitidis infection

• Hemophilia or other bleeding diatheses.

• Autoimmune disorders; mild autoimmune disorders, such as eczema, are not exclusionary and will be determined by the study physician.

• Unstable psychiatric condition (defined as receiving either <3 months of the same medication (and dose) or a decompensating event during the previous 3 months) or psychiatric condition that, in the opinion of the investigator, will compromise the participant's ability to comply with protocol requirements

• Known anatomic abnormality of the urethra or urethral meatus (granular hypospadias is not exclusionary if the study physician believes that the urethral location will not interfere with inoculation catheter insertion)

• Any immunization in 28 days prior to enrollment

• Self-reported treatment for cancer within the past year

• Receipt of anticoagulants (aspirin or nonsteroidal anti-inflammatory drugs (NSAIDS) are acceptable) within 14 days prior to study entry.

• Use of any systemic immunomodulatory treatment, systemic corticosteroids, (inhaled and topical corticosteroids acceptable), investigational products, interleukins, interferons, growth factors, or intravenous immunoglobulin (IVIG) within 45 days prior to study entry.

• Have donated blood or blood products within 28 days before study vaccination, plan to donate blood at any time during the study and up to 28 days after the last blood draw.

• Allergy to penicillin, cephalosporins or ciprofloxacin or to lidocaine or any component of 4C-MenB vaccine or control vaccines (flu, Influenza vaccine (FLULAVALTM) and Td, TDVAXTM), including latex (confirmed delayed contact hypersensitivity to latex is not exclusionary)

• Treatment with medications that are contraindicated with cefixime, ceftriaxone or ciprofloxacin and that cannot be withheld for the single doses given in this study

• Serum creatinine level > 1.1X upper limit of normal (ULN) and deemed clinically significant by the study physician

• Serum ALT level > 1.25X ULN and deemed clinically significant by the study physician

• WBC count < 2.5 or > 15.0 x109/L and deemed clinically significant by the study physician

• Absolute neutrophil count (ANC) < 1.0 x 109/L and deemed clinically significant by the study physician

• Hemoglobin level < 11.0 g/dL or above ULN and deemed clinically significant by the study physician

• Urinalysis: Qualitative protein level ≥ 1+ or Red blood cell (RBC) count≥ 6/hpf

• Any condition in the opinion of the investigator that would interfere with the proper conduct of the trial.

Medications not permitted with cefixime or ceftriaxone:

Warfarin Probenecid Aspirin Diuretics such as furosemide Aminoglycoside antibiotics Chloramphenicol

Medications not permitted with ciprofloxacin:

Tizanidine Theophylline Warfarin Glyburide Cyclosporine Probenecid Phenytoin Methotrexate Antacids, multivitamins, and other dietary supplements containing magnesium, calcium, aluminum, iron or zinc Caffeine-containing medications Sucralfate or didanosine chewable or buffered tablets